Variation in responses to stress can underlie or exacerbate psychiatric illness and social disorders. During stress, activity within the amygdala of the brain appears to alter monoamine neurotransmitter activity in the medial prefrontal cortex (mPFC), and neurotransmission within the mPFC contributes to the cognitive and endocrine processes associated with coping in stressful situations. Currently, how the amygdala alters neurotransmission in the mPFC is not well understood. Also, the specific role of the monoamine serotonin in the mPFC during stress is unclear. This project aims to determine how the neural output from the amygdala is integrated in other brain regions to alter mPFC monoamine activity, and also examine the behavioral consequences of this neural activity. It is anticipated that such knowledge will provide greater understanding of the neural circuitry thought to mediate stress, and advance research directed at designing pharmacological interventions to modulate stress responsiveness in psychiatric or social disorders. The proposed studies will initially map out brain pathways by which the amygdala stimulates monoamine activity in the mPFC, using in vivo chronoamperometry within a rat model. This will involve electrical stimulation of the amygdala in anaesthetized rats, with resultant monoamine release recorded from the mPFC before and after transient blockade of pathways with the sodium channel blocker lidocaine. Subsequent experiments using a similar methodology will determine the involvement of the neurohormone corticotrophin releasing factor (CRF) in activating these pathways as CRF increases during stress, and is a major neurotransmitter used by the output neurons of the amygdala. Specifically, the effects of a CRF blocker on amygdala-elicited changes in mPFC monoamine release will be assessed. It is expected that results will determine whether targeting CRF release or transmission in the brain will provide a useful and feasible direction for pharmaceutical therapeutics. The final experiments will assess whether pharmacological alterations (both increases and decreases) in serotoninergic activity within the mPFC change behavioral responsiveness towards an acute stressor, using microdialysis in freely moving rats. Positive findings here will provide essential information as to the role of serotonin in stress, and offer options for the 'fine-tuning' of pharmacological therapeutics to limit stress responsiveness and aid rehabilitation.